Biosensor calibration structure containing different sensing surface area

ABSTRACT

A biosensor calibration structure is provided that includes at least two electrode structures in which at least one of the electrode structures has a non-random nanopattern on the sensing surface which provides a different sensing surface area than at least one other electrode structure. The at least one other electrode structure may be non-patterned (i.e., flat) or have another non-random nanopattern on the sensing surface. A biological functionalization material such as, for example, glucose oxidase or glucose dehydrogenase, can be located on at least the sensing surface of each electrode structure. The biosensor calibration structure can be used within a biosensor calibration method.

BACKGROUND

The present application relates to biosensors for use in medical andenvironmental monitoring. More particularly, the present applicationrelates to a biosensor calibration structure that includes at least twoelectrode structures in which at least one of the electrode structureshas a non-random nanopattern on the sensing surface which provides adifferent sensing surface area than at least one other electrodestructure. The present application also relates to a calibration methodthat employs the biosensor calibration structure of the presentapplication.

Biosensors with enhanced signal and sensitivity are essential to providereliable data for both medical and environmental monitoring. Suchbiosensors are especially needed for areas related to food and watersupply security as well as the healthcare industry. For healthcare,glucose sensors comprise a significant portion of the existing biosensormarket. Platinum (Pt) is commonly used as a working electrode in glucosesensors, and platinum has demonstrated biocompatibility. Externalelectrochemical sensors (so-called “Test-Strips”) are commonly used.However, limitations exist on the accuracy and applicability of teststrip sensors.

In vivo glucose sensors, which are implanted into a human body, can beused to continuously monitor blood sugar. However, the foreign bodyresponse restricts the functionality of in vivo biosensors. Moreover,the foreign body response can reduce the sensor signal output over time.In some applications, the foreign body response may even reject thebiosensor from the human body.

For biosensors used in vivo or in other environments in which sensorstability could be at risk, effective methods of real-time sensorcalibration are essential to provide reliable sensor outputs that can betrusted for decision making. For example, as in vivo sensor signaldegrades to encapsulation as part of the foreign body response,validating the calibration accuracy becomes more of a challenge. Inorder to improve sensor calibration accuracy, commercial manufactures ofin vivo glucose sensors are shifting their calibration strategies to usemultiple electrodes of a same material or a different material as ameans for calibration. Although such techniques improve, to some degree,the sensor accuracy and useful lifetime, the formation of multipleelectrodes (specifically of different materials) is time consuming andincreases the cost associated with the production process. There is thusa need to provide a structure that can be used in biosensor calibrationthat has enhanced accuracy, increased useful lifetime, and is costefficient to manufacture.

SUMMARY

A biosensor calibration structure is provided that includes at least twoelectrode structures in which at least one of the electrode structureshas a non-random nanopattern on the sensing surface which provides adifferent sensing surface area than at least one other electrodestructure. The at least one other electrode structure may benon-patterned (i.e., flat) or have another non-random nanopattern on thesensing surface. In some embodiments, a biological functionalizationmaterial such as, for example, glucose oxidase or glucose dehydrogenase,can be located on at least the sensing surface of each electrodestructure. The biosensor calibration structure of the presentapplication enables a hardware-based calibration method that maintainsand, in some instances, enhances, sensor signal throughout the lifetimeof the structure.

In one aspect of the present application, a biosensor calibrationstructure is provided. In one embodiment of the present application, thebiosensor calibration structure may include an array of electrodestructures each having a sensing surface, wherein at least one of theelectrode structures of the array of electrode structures has anon-random nanopattern on the sensing surface which provides a differentsensing surface area than at least one other electrode structure in thearray of electrode structures.

In another aspect of the present application, a calibration method isprovided. In one embodiment of the present application, the calibrationmethod may include providing an array of electrode structures eachhaving a sensing surface, wherein at least one of the electrodestructures of the array of electrode structures has a non-randomnanopattern on the sensing surface which provides a different sensingsurface area than at least one other electrode structure in the array ofelectrode structures. Next, a signal generated by each electrodestructure of the array of electrode structures in the presence of ananalyte is observed. Each signal is then compared and thereafter theanalyte concentration is computed utilizing the comparison of signaldata obtained from the sensing surface area of each of the electrodestructures.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1A is a top-down view of a first exemplary biosensor calibrationstructure that can be employed in the present application.

FIG. 1B is a cross-sectional view illustrating one of the rows of thefirst exemplary biosensor calibration structure shown in FIG. 1A.

FIG. 2A is a top-down view of a second exemplary biosensor calibrationstructure that can be employed in the present application.

FIG. 2B is a cross-sectional view illustrating one of the rows of thefirst exemplary biosensor calibration structure shown in FIG. 2A.

FIG. 3 is a cross sectional view of a third exemplary biosensorcalibration structure that can be employed in the present application.

FIG. 4 is cross sectional view illustrating one of the electrodestructures of one of the biosensor calibration structures of the presentapplication after providing a biological functionalization material onat least the sensing surface of the electrode structure.

DETAILED DESCRIPTION

The present application will now be described in greater detail byreferring to the following discussion and drawings that accompany thepresent application. It is noted that the drawings of the presentapplication are provided for illustrative purposes only and, as such,the drawings are not drawn to scale. It is also noted that like andcorresponding elements are referred to by like reference numerals.

In the following description, numerous specific details are set forth,such as particular structures, components, materials, dimensions,processing steps and techniques, in order to provide an understanding ofthe various embodiments of the present application. However, it will beappreciated by one of ordinary skill in the art that the variousembodiments of the present application may be practiced without thesespecific details. In other instances, well-known structures orprocessing steps have not been described in detail in order to avoidobscuring the present application.

It will be understood that when an element as a layer, region orsubstrate is referred to as being “on” or “over” another element, it canbe directly on the other element or intervening elements may also bepresent. In contrast, when an element is referred to as being “directlyon” or “directly over” another element, there are no interveningelements present. It will also be understood that when an element isreferred to as being “beneath” or “under” another element, it can bedirectly beneath or under the other element, or intervening elements maybe present. In contrast, when an element is referred to as being“directly beneath” or “directly under” another element, there are nointervening elements present.

The present application provides biosensor calibration structures whichinclude an array of electrode structures each having a sensing surface,wherein at least one of the electrode structures of the array ofelectrode structures has a non-random nanopattern on the sensing surfacewhich provides a different sensing surface area than at least one otherelectrode structure in the array of electrode structures. A nanopatternconsists of a series of repeating feature elements with a criticalfeature size of less than one micron in dimension. The electrodestructures of the array of electrode structures that have the non-randomnanopattern provide a controlled variation in the surface area which isactive for sensing. The known difference in sensing surface area may betranslated to a known difference in senor signal. Since the sensorsurface area should remain constant and not vary with time or usagethroughout the lifetime of the sensor, the difference in signal betweenelectrodes with known surface area variations should also remainconstant throughout the sensor. If the signal difference between theelectrodes with known surface area does not remain constant, theresulting variation in signal difference can be used to identify anissue with the sensor function or calibration. A real-time calculationcan be completed to identify the delta in signal difference between theelectrodes, and mathematical adjustment may be completed to compensatefor the observed delta in signal difference. Therefore quantifyingdeviations from the known signal difference between the electrodes canbe employed as a sensor calibration mechanism.

Referring first to FIGS. 1A-1B, there are shown a first exemplarybiosensor calibration structure that can be employed in one embodimentof the present application. The first exemplary structure shown in FIGS.1A-1B includes an array of electrode structures 10A, 10B, 10C and 10D.The array of electrode structures shown in FIGS. 1A-1B is typicallyformed upon a substrate (not shown). The substrate is composed of anymaterial. In one example, the substrate is composed of a material thatis compatible for inserting into the human body. Although the presentapplication describes and illustrates four electrode structures withinthe array of electrode structures, the present application is notlimited to that number of electrode structures. Instead, the presentapplication can be used with any number of electrode structures providedthat at least one of the electrode structures of the array of electrodestructures has a non-random nanopattern on the sensing surface whichprovides a different sensing surface area than at least one otherelectrode structure in the array of electrode structures. Thus, theminimum number of electrode structures within the array of electrodestructures is two. In this embodiment of the present application, thedensity/pitch of the non-random nanopattern of each individual electrodestructure in the array of electrode structures is altered to providedifferent sensing surface area. The term “sensing surface area” is usedthroughout the present application to denote the surfaces of theelectrode structure which are exposed to the substance or solutioncontaining the substance to be sensed.

In the embodiment illustrated in FIGS. 1A-1B and by way of one example,the density of the non-random nanopattern feature elements of theelectrode structure within the array of electrode structures decreasesfrom left to right. Conversely, and in the embodiment illustrated inFIGS. 1A-1B, the pitch, P (denoted by the double-headed arrow), betweeneach neighboring non-random nanopattern of the electrode structureswithin the array of electrode structures increases from left to right.Pitch is defined as the minimum distance between repeatable elementswhich comprise the nanopattern.

In the example shown for the first exemplary biosensor calibrationstructure, electrode structures 10A, 10B and 10C have a non-randomnanopattern located on a sensing surface, while electrode structure 10Ddoes not have any non-random nanopattern located on a sensing surface(thus the electrode structure 10D is flat). Each of the electrodestructures (i.e., electrode structure 10A, 10B and 10C) that has anon-random nanopattern located on a sensing surface comprises anelectrode base structure 12 having non-random topography (defined by thenon-random, i.e., regular repeating, individual features 14). Theelectrode structure 10D merely includes an electrode base structure 12.In an ideal embodiment, the nanopatterns depicted in 10A, 10B, and 10Cwould be comprised of features with a constant height, feature crosssection, and material composition. Therefore, electrode structure 10Ahas a greater surface area for active sensing compared to electrodestructure 10B, with electrode structure 10B having a greater sensingsurface area compared to electrode structure 10C, and electrodestructure 10C with a greater sensing surface area compared to electrodestructure 10D.

Referring now to FIGS. 2A-2B, there are illustrated a second exemplarybiosensor calibration structure that can be employed in one embodimentof the present application. The array of electrode structures shown inFIGS. 2A-2B is typically formed upon a substrate (not shown). Thesubstrate is composed of any material. In one example, the substrate iscomposed of a material that is compatible for inserting into the humanbody. The second exemplary structure shown in FIGS. 2A-2B also includesan array of electrode structures 20A, 20B, 20C and 20D. Although thepresent application describes and illustrates four electrode structureswithin the array of electrode structures, the present application is notlimited to that number of electrode structures. Instead, and asmentioned above, the present application can be used with any number ofelectrode structures provided that at least one of the electrodestructures of the array of electrode structures has a non-randomnanopattern on the sensing surface which provides a different sensingsurface area than at least one other electrode structure in the array ofelectrode structures.

In this embodiment of the present application, the cross section size ordiameter of the non-random nanopattern feature element of eachindividual electrode structure in the array of electrode structures isaltered to provide different sensing surface area. In the embodimentillustrated in FIGS. 2A-2B and by way of one example, the cross sectionsize/diameter of the non-random nanopatterns of the electrode structurewithin the array of electrode structures increases from left to right.

In the example shown for the second exemplary biosensor calibrationstructure, electrode structures 20A, 20B and 20C have a non-randomnanopattern located on a sensing surface, while electrode structure 20Ddoes not have any non-random nanopattern located on a sensing surface(thus the electrode structure 20D is flat). Each of the electrodestructures (i.e., electrode structure 20A, 20B and 20C) that has anon-random nanopattern located on a sensing surface comprises anelectrode base structure 12 having non-random topography (defined by thenon-random, i.e., regular repeating, individual features 14). Theelectrode structure 20D merely includes an electrode base structure 12.In an ideal embodiment, the nanopatterns depicted in 20A, 20B, and 20Cwould be comprised of features with a constant height, pitch, andmaterial composition. Therefore, electrode structure 20C has a greatersurface area for active sensing compared to electrode structure 20B,with electrode structure 20B having a greater sensing surface areacompared to electrode structure 20A, and electrode structure 20A with agreater sensing surface area compared to electrode structure 20D.

Referring now to FIG. 3, there is illustrated a third exemplarybiosensor calibration structure that can be employed in one embodimentof the present application. The array of electrode structures shown inFIG. 3 is typically formed upon a substrate (not shown). The substrateis composed of any material. In one example, the substrate is composedof a material that is compatible for inserting into the human body. Thethird exemplary structure shown in FIG. 3 also includes an array ofelectrode structures 30A, 30B, 30C and 30D. Although the presentapplication describes and illustrates four electrode structures withinthe array of electrode structures, the present application is notlimited to that number of electrode structures. Instead, the presentapplication can be used with any number of electrode structures providedthat at least one of the electrode structures of the array of electrodestructures has a non-random nanopattern on the sensing surface whichprovides a different sensing surface area than at least one otherelectrode structure in the array of electrode structures.

In this embodiment of the present application, the height or aspectratio of the non-random nanopattern feature element of each individualelectrode structure in the array of electrode structures is altered toprovide different sensing area. In the embodiment illustrated in FIG. 3and by way of one example, the height or aspect ratio (i.e., ratio ofwidth to height) of the non-random nanopatterns of the electrodestructures 30A, 30B and 30C increases from left to right.

In the example shown for the third exemplary biosensor calibrationstructure, electrode structures 30A, 30B and 30C have a non-randomnanopattern located on a sensing surface, while electrode structure 30Ddoes not any have non-random nanopattern located on a sensing surface(thus the electrode structure 30D is flat). Each of the electrodestructures (i.e., electrode structure 30A, 30B and 30C) that has anon-random nanopattern located on a sensing surface comprises anelectrode base structure 12 having non-random topography (defined by thenon-random, i.e., regular repeating, individual features 14). Theelectrode structure 30D merely includes an electrode base structure 12.In an ideal embodiment, the nanopatterns depicted in 30A, 30B, and 30Cwould be comprised of features with a constant feature cross section,pitch, and material composition. Therefore, electrode structure 30C hasa greater surface area for active sensing compared to electrodestructure 30B, with electrode structure 30B having a greater sensingsurface area compared to electrode structure 30A, and electrodestructure 30A with a greater sensing surface area compared to electrodestructure 30D.

In some embodiments and for the electrode structures that have anon-random nanopattern of FIGS. 1A, 1B, 2A, 2B and 3, the electrode basestructure 12 and the non-random topography (i.e., the non-randomindividual articulated features 14) are of uniform construction (i.e.,single piece) and uniform composition. That is, such electrodestructures lack an interface between the electrode base structure 12 andthe non-random individual articulated features 14 that collectivelydefine the non-random topography of the electrode structure. In analternate embodiment, the electrode structures may be formed of the samecomposition in a construction which features an interface between thenon-random individual articulated features 14 and the electrode basestructure 12. In yet another embodiment, the individual articulatedfeatures 14 and the electrode base structure 12 may be comprised ofdifferent materials which may result in an interface between theelectrode base structure 12 and the non-random individual articulatedfeatures 14.

The shape of the electrode base structure 12 is not limited to anyspecific shape. In one embodiment of the present application, the shapeof the electrode base structure 12 is a polygonal. In such anembodiment, the shape of the electrode base structure 12 may betriangular, quadrilateral or pentagonal. In other embodiments, the shapeof the electrode base structure 12 may be circular or elliptical. Theshape of the electrode base structure 12 may also include additionalstructures such as wiring or probe pads required to read out theelectrical signal from each individual electrode structure.

Each non-random individual articulated feature 14 that provides thenon-random topography and the non-random nanopattern of the electrodestructure has a size that is less than the size of the electrode basestructure 12. Each non-random individual articulated feature 14 may havevarious shapes and sizes. For example, each non-random individualarticulated feature 14 may have a shape of a rod, a cone, an ellipse, oran annular structure. In one embodiment of the present application, eachnon-random individual articulated feature 14 may have a criticaldimension ranging in size from 5 nm to 900 nm. In another embodiment ofthe present application, each non-random individual articulated feature14 may have a critical dimension ranging in size from 20 nm to 300 nm.In one embodiment of the present application, each non-random individualarticulated feature 14 has a pitch ratio of from 2:1 to 100:1. Inanother embodiment of the present application, each non-randomindividual articulated feature 14 has a pitch ratio of from 2:1 to 20:1.

In one embodiment of the present application, each non-random individualarticulated feature 14 has a height from 5 nm to 300 μm. In anotherembodiment of the present application, each non-random individualarticulated feature 14 has a height from 50 nm to 20 μm. In oneembodiment of the present application, each non-random individualarticulated feature 14 has an aspect ratio (i.e., ratio of width toheight) of 1:1 to 500:1. In another embodiment of the presentapplication, each non-random individual articulated feature 14 has anaspect ratio (i.e., width to height) of 2:1 to 100:1.

Each electrode structure of the array of electrode structures of thepresent application including the electrode base structure 12 and, whenpresent, each non-random individual articulated feature 14 that providesthe non-random topography of at least one of the electrode structureswithin an array of electrode structures is composed of an electricallyconductive material (hereinafter just “conductive material”). In oneembodiment of the present application, the electrically conductivematerial is a metallic glass. By “metallic glass” it is meant a solidmetallic material, usually an alloy, with a disordered amorphous atomicstructure. Metallic glasses can also be referred to herein as amorphousmetals or glassy metals. In the case where the conductive material is ametallic glass, the conductive material can be non-crystalline oramorphous. In some embodiments, the metallic glass that can be used asthe conductive material may include an element selected from platinum,copper, nickel, phosphorous, palladium, zirconium, silver, aluminum,carbon or alloy or alloys thereof. In one example, the electrodestructure of the present application may be composed of a platinum-basedbulk metallic glass alloy such as, but not limited to, a PtCuNiP alloy.

In some embodiments, the conductive material that provides the electrodestructures is a conductive metal-containing material including, but notlimited to, platinum, copper, silver, gold, tungsten, aluminum, iron,palladium, nickel, titanium, or zirconium. Alloys of these metals mayalso be employed as the conductive metal-containing material that canprovide electrode structures of the array of electrode structures.

The electrode structures can be formed utilizing various techniques. Inone embodiment of the present application, electrode structures havingthe non-random nanopatterns may be formed by first providing a moldhaving a pattern that comprises both an electrode base structure shapeand a nanotopography shape. By “nanotopography shape” is meant an arrayof non-random (i.e., regular repeating) individual articulated featureswhose size is less than the size of the electrode base structure shapeof the mold. The mold may be composed of any material including forexample, a semiconductor material and/or a dielectric material. The moldmay be formed by lithography and etching. A conductive material is thenformed into the mold. In some embodiments, a metallic seed layer may beformed into the mold prior to forming the conductive material In oneembodiment, an amorphous metal, which may also be referred to as a“metallic glass” or a “bulk metallic glass,” is introduced into the moldby utilizing a thermoplastic forming process to provide an electrodestructure comprising the amorphous metal (i.e., metallic glass) andhaving the electrode base structure shape and the nanotopography shaperesulting from the influence of the mold. In another embodiment, theconductive material that provides the mold may include a conductivemetal-containing material as defined above that is electrodeposited on asurface of a metallic seed layer that is provided on the mold. Afterforming at least the conductive material into the mold and removing anyexcess conductive material formed outside of the mold, the mold is thenremoved from the resultant electrode structure utilizing means wellknown to those skilled in the art.

In another embodiment, electrode structures having the non-randomnanopatterns can be formed by first providing an electrode structurecomprising a conductive material. Thereafter, lithography and etchingcan be used to provide the electrode structures with non-randomtopography.

In yet another embodiment, electrode structures having the non-randomnanopatterns can be formed by providing an electrode base structurehaving an electrode base structure shape on a substrate. Next, apatterned material layer is formed surrounding the electrode base,wherein the patterned material layer contains openings for defining ananotopography shape of the electrode structure. A metallic seed layercan then be formed on exposed surfaces of the electrode base structureand within the openings of the patterned material layer, and thereaftera conductive metal-containing material is electroplated on the metallicseed layer and within the openings of the patterned material layer toprovide the electrode structure comprising the electrode base structurehaving the electrode base structure shape and the conductivemetal-containing material having the nanotopography shape.

In further embodiment, electrode structures having the non-randomnanopatterns can be formed by an electrode base structure material on asubstrate. Next, a patterned material layer is formed surrounding theelectrode base structure material, wherein the patterned material layercontains openings. The electrode base structure material exposed surfaceis then etched utilizing the patterned material layer as anetch-resistant mask to provide the electrode structure comprising aremaining portion of the electrode base structure material and having anelectrode base structure shape and a nanotopography shape. The patternedmaterial layer is then removed.

Details concerning any of the above mentioned fabrication process can befound, for example, in U.S. Ser. No. 15/005,690, filed Jan. 25, 2016,U.S. Ser. No. 15/218,550, filed Jul. 25, 2016 and U.S. Ser. No.15/419,524, filed Jan. 20, 2017, the entire contents of each areincorporated herein by reference. Electrode structures having a flatsurface can be formed utilizing any well known technique.

After forming the array of electrode structures and, in order tofunctionalize the structure to respond as a biosensor, a biologicalfunctionalization material can be applied to the surface of theelectrode structures including each non-random individual articulatedfeature 14 that provides the nanotopography shape; for electrodestructures that are flat, the biological functionalization material canbe formed directly onto a physically exposed flat surface. Any of theexposed areas of the electrode base structure 12 may also be coated withthe biological functionalization material. FIG. 4 represents oneelectrode structure shown in cross section having a non-randomnanopattern that can be present in one of the biosensor calibrationstructures of the present application after providing biologicalfunctionalization material 16 on at least the sensing surface of eachelectrode structure of the array of electrode structures.

By “biological functionalization material” it is meant any bioreceptorthat binds with a complementary target biomolecule to create a bindingevent. In some embodiments, biochemical reactions involving thebiological functionalization material generate an electrical signalwhich can be conducted by the non-random individual articulated features14 of the electrode structures under an applied electric potential.Examples of biological functionalization materials that can be used inthe present application include an oligonucleotide, a nucleic acid, apeptide, a ligand, a protein, an enzyme, or any other material apt tobind with a complementary target biomolecule. When the electrodestructures within the array of electrode structures are used for glucosesensing, the biological functionalization material can be composed ofglucose oxidase or glucose dehydrogenase.

The biological functionalization material can be applied to theelectrode structures utilizing established biological functionalizationprocesses known to those skilled in the art. Such biologicalfunctionalization processes typically include a series of chemicalreactions that attach the biological functionalization material on thesurface of the electrode structure.

The array of electrode structures can be used as a component in variousbiosensors which include other well-known components, such as but notlimited to, reference and counter electrode structures.

The calibration electrode structures of the present application can beused in a calibration method to improve sensor signal and signalsensitivity as well as the accuracy of the signal. The calibrationmethod may include providing an array of electrode structures eachhaving a sensing surface, wherein at least one of the electrodestructures of the array of electrode structures has a non-randomnanopattern on the sensing surface which provides a different sensingsurface area than at least one other electrode structure in the array ofelectrode structures. In some embodiments, a biologicalfunctionalization material, as defined above may be applied to thesensing surface of each electrode structure within the array ofelectrode structures. Next, a signal generated by each electrodestructure of the array of electrode structures in the presence of ananalyte is observed. In some embodiments, the analyte is present in ahuman body. Each signal is then compared and thereafter the analyteconcentration is computed utilizing the comparison of signal datedobtain from each electrode structure of the area of electrodestructures. If the signal difference between the electrodes with knownsurface area does not remain constant, the resulting variation in thesignal difference can be used to identify an issue with the sensorfunction or calibration. A real-time calculation can be completed toidentify the delta in signal difference between the electrodes, andmathematical adjustment may be completed to compensate for the observeddelta in signal difference. The comparison and analyte concentrationcalculation can be performed by hand or utilizing a computer system.

The term “analyte” is used to refer to a substance or chemicalconstituent such as a biological fluid (for example, blood, interstitialfluid, cerebral spinal fluid, lymph fluid, or urine) that can beanalyzed. Analytes can include naturally occurring substances,artificial substances, metabolites, and/or reaction products. In someembodiments, the analyte for measurement by the sensing areas isglucose. However, other analytes are contemplates as well, including,but not limited to lactate, salts, sugars, proteins, fats, vitamins, andhormones naturally occurring in the blood or interstitial fluids canconstitute analytes in certain embodiments. The analyst can be naturallypresent in biological fluid or endogenous; for example, a metabolicproduct, a hormone, and antigen, and an antibody. Alternatively, theanalyte can be introduced into the body or exogeneous, for example, acontrast agent for imaging, a radioisotope, a chemical agent, a ceuticalcomposition including, but not limited to insulin. The metabolic fordrugs and pharmaceutical compositions are also contemplated as analytes.

In some embodiments, a computer or processing system may be used in thecalibration method in one embodiment of the present disclosure. Notably,the computer system may be used to run the calibration method and/orproviding various other functions such as calculations, comparisons,etc. The computer system is only one example of a suitable processingsystem and is not intended to suggest any limitation as to the scope ofuse or functionality of embodiments of the methodology described herein.The processing system shown may be operational with numerous othergeneral purpose or special purpose computing system environments orconfigurations. Examples of well-known computing systems, environments,and/or configurations that may be suitable for use with the processingsystem may include, but are not limited to, personal computer systems,server computer systems, thin clients, thick clients, handheld or laptopdevices, multiprocessor systems, microprocessor-based systems, set topboxes, programmable consumer electronics, network PCs, minicomputersystems, mainframe computer systems, and distributed cloud computingenvironments that include any of the above systems or devices, and thelike.

The biosensor calibration structure of the present application can beoperatively coupled to a variety of other systems elements typicallyused with analyte sensors (e.g., structural elements such as piercingmembers, insertion sets and the like as well as electronic componentssuch as processors, monitors, medication infusion pumps and the like),for example to adapt them for use in various contexts (e.g.,implantation within a mammal). One embodiment includes monitoring aphysiological characteristic of a user using the biosensor calibrationstructure of the present application. In typical embodiments, theprocessor determines a dynamic behavior of the physiologicalcharacteristic value and provides an observable indicator based upon thedynamic behavior of the physiological characteristic value sodetermined. In some embodiments, the physiological characteristic valueis a measure of the concentration of blood glucose in the user. In otherembodiments, the process of analyzing the received signal anddetermining a dynamic behavior includes repeatedly measuring thephysiological characteristic value to obtain a series of physiologicalcharacteristic values in order to, for example, incorporate comparativeredundancies into a sensor apparatus in a manner designed to provideconfirmatory information on sensor function, analyte concentrationmeasurements, the presence of interferences and the like.

Embodiments include devices which display data from measurements of asensed physiological characteristic (e.g., blood glucose concentrations)in a manner and format tailored to allow a user of the device to easilymonitor and, if necessary, modulate the physiological status of thatcharacteristic (e.g., modulation of blood glucose concentrations viainsulin administration). An illustrative embodiment is a devicecomprising a sensor input capable of receiving a signal from a sensor,the signal being based on a sensed physiological characteristic value ofa user; a memory for storing a plurality of measurements of the sensedphysiological characteristic value of the user from the received signalfrom the sensor; and a display for presenting a text and/or graphicalrepresentation of the plurality of measurements of the sensedphysiological characteristic value (e.g., text, a line graph or thelike, a bar graph or the like, a grid pattern or the like or acombination thereof). Typically, the graphical representation displaysreal time measurements of the sensed physiological characteristic value.Such devices can be used in a variety of contexts, for example incombination with other medical apparatuses. In some embodiments of theinvention, the device is used in combination with at least one othermedical device.

An illustrative system embodiment consists of a glucose sensor, atransmitter and pump receiver and a glucose meter. In this system, radiosignals from the transmitter can be sent to the pump receiverperiodically (e.g., every 5 minutes) to provide providing real-timesensor glucose (SG) values. Values/graphs are displayed on a monitor ofthe pump receiver so that a user can self monitor blood glucose anddeliver insulin using their own insulin pump. Typically an embodiment ofdevice disclosed herein communicates with a second medical device via awired or wireless connection. Wireless communication can include forexample the reception of emitted radiation signals as occurs with thetransmission of signals via RF telemetry, infrared transmissions,optical transmission, sonic and ultrasonic transmissions and the like.Optionally, the device is an integral part of a medication infusion pump(e.g., an insulin pump). Typically in such devices, the physiologicalcharacteristic values include a plurality of measurements of bloodglucose.

While the present application has been particularly shown and describedwith respect to preferred embodiments thereof, it will be understood bythose skilled in the art that the foregoing and other changes in formsand details may be made without departing from the spirit and scope ofthe present application. It is therefore intended that the presentapplication not be limited to the exact forms and details described andillustrated, but fall within the scope of the appended claims.

What is claimed is:
 1. A biosensor calibration structure comprising: anarray of electrode structures each having a sensing surface, wherein atleast one of the electrode structures of the array of electrodestructures has a non-random nanopattern on the sensing surface whichprovides a different sensing surface area than at least one otherelectrode structure in the array of electrode structures.
 2. Thebiosensor calibration structure of claim 1, wherein the at least oneother electrode structure of the array of electrode structures isnon-patterned.
 3. The biosensor calibration structure of claim 1,wherein each electrode structure of the array of electrode structurescomprises an electrically conductive material.
 4. The biosensorcalibration structure of claim 1, wherein the at least one of theelectrode structures having the non-random nanopattern comprises anelectrode base structure having topography.
 5. The biosensor calibrationstructure of claim 4, wherein the electrode base structure and thetopography are of uniform construction and comprise a same electricallyconductive material.
 6. The biosensor calibration structure of claim 5,wherein the electrode base structure comprises an electricallyconductive material that differs from an electrically conductivematerial that comprises the topography.
 7. The biosensor calibrationstructure of claim 4, wherein the topography comprises rods, cones, orannular structures.
 8. The biosensor calibration structure of claim 1,wherein the at least one other electrode structure of the array ofelectrode structures has another non-random nanopattern on the sensingsurface.
 9. The biosensor calibration structure of claim 8, wherein theanother non-random nanopattern of the at least one other electrodestructure has a different density than the non-random nanopattern of theat least one of the electrode structures of the array of electrodestructures.
 10. The biosensor calibration structure of claim 8, whereinthe another non-random nanopattern of the at least one other electrodestructure has a different cross sectional size than the non-randomnanopattern of the at least one of the electrode structures of the arrayof electrode structures.
 11. The biosensor calibration structure ofclaim 8, wherein the another non-random nanopattern of the at least oneother electrode structure has a different aspect ratio than thenon-random nanopattern of the at least one of the electrode structuresof the array of electrode structures.
 12. The biosensor calibrationstructure of claim 1, further comprising a biological functionalizationmaterial located on at least the sensing surface of each electrodestructure of the array of electrode structures.
 13. The biosensorcalibration structure of claim 12, wherein the biologicalfunctionalization material is composed of an oligonucleotide, a nucleicacid, a peptide, a ligand, a protein, an enzyme, or any other materialapt to bind with a complementary target biomolecule.
 14. The biosensorcalibration structure of claim 13, wherein the biologicalfunctionalization material is composed of glucose oxidase or glucosedehydrogenase.
 15. A calibration method comprising: providing an arrayof electrode structures each having a sensing surface, wherein at leastone of the electrode structures of the array of electrode structures hasa non-random nanopattern on the sensing surface which provides adifferent sensing surface area than at least one other electrodestructure in the array of electrode structures; observing a signalgenerated by each electrode structure of the array of electrodestructures in the presence of an analyte; comparing each signal; andcomputing an analyte concentration utilizing the comparison of signaldata obtained from the sensing surface area of each of the electrodestructures.
 16. The calibration method of claim 15, wherein prior toobserving the signal a biological functionalization material is formedon at least the sensing surface of each electrode structure of the arrayof electrode structures.
 17. The calibration method of claim 16, whereinthe biological functionalization material is composed of anoligonucleotide, a nucleic acid, a peptide, a ligand, a protein, anenzyme, or any other material apt to bind with a complementary targetbiomolecule.
 18. The calibration method of claim 16, wherein thebiological functionalization material is composed of glucose oxidase orglucose dehydrogenase.
 19. The calibration method of claim 15, whereinthe at least one other electrode structure of the array of electrodestructures is flat.
 20. The calibration method of claim 15, wherein theat least one other electrode structure of the array of electrodestructures has another non-random nanopattern on the sensing surface,wherein the another non-random nanopattern of the at least one otherelectrode structure has a different density, different cross sectionalsize, or different aspect ratio than the non-random nanopattern of theat least one of the electrodes of the array of electrodes.